By Christopher Snowbeck
It's bad enough to have a child diagnosed with cancer.
It's even worse when doctors say the cancer treatments they would normally prescribe must be altered because of a drug shortage.
That situation confronted Brian and Justine Zirbes of Crystal last spring as their son Axel neared a treatment date at Children's Hospitals & Clinics of Minnesota.
Like other cancer centers, Children's found itself caught in the middle of an ongoing shortage of certain medicines, including many injected chemotherapy drugs. Doctors told the Zirbeses that because of a shortage, they would need to find a substitute for several doses of the drug Ara-C or cytarabine, which prevents leukemia cells from growing in spinal fluid.
"I was like: 'No, I don't like that. There have never been any studies of that (other) drug's effectiveness,' " recalled Justine Zirbes. "I rose a stink and said: 'Tell me what I need to do to get the Ara-C. I'll drive to Canada if I need to.' "
At the eleventh hour, Children's was able to find the drug for Axel. He is now 4, and his parents are hopeful about his prognosis - most children with Axel's type of cancer are cured, so long as they stick to a particular treatment protocol.
But close calls like Axel's have become more common since 2010 as drug shortages in the United States have surged. In 2006, there were 70 drug shortages, according to the American Society of Health System Pharmacists, but the tally last year reached 267.
LAWMAKERS TAKE NOTICE
Federal lawmakers increasingly are paying attention.
Sen. Amy Klobuchar, D-Minn., introduced legislation last February that would require drug companies to give the FDA more notice about potential shortage problems, and Sen. Orrin Hatch, R-Utah, has talked about finding ways to address some of the economic sources of the problem.
But many are pessimistic that a quick fix will be found.
"I think shortages are going to be with us for a while," said Bona Benjamin, director of medication-use quality improvement for the American Society of Health System Pharmacists. "There isn't just one single solution that's going to turn the tide quickly."
In many cases, drugs are in short supply because manufacturers have suspended production to deal with quality-control problems. In other cases, drug companies can't find a supply of the ingredients they need to make certain medications.
The drug shortages have been highly concentrated among generic drugs that are injected medicines, according to a November report from IMS Health, a health care information company. While such drugs account for a small part of the medication market, many, such as cytarabine - the drug Axel Zirbes needed - are critical for treating cancer, cardiovascular disease and central nervous system conditions, according to the report.
Prices for some of these generic drugs are so low that only a few manufacturers can afford to produce the medications, said Stephen Schondelmeyer, a professor of pharmaceutical economics at the University of Minnesota. So, when a drug manufacturer has a quality-control problem, there aren't enough other suppliers in the market to fill the gap, Schondelmeyer said.
"Each drug shortage has its own story," Schondelmeyer added. "While there are many similarities, there are also many differences....This is a very multifaceted problem."
Although shortages of chemotherapy drugs have gotten the most attention in recent years, those aren't the supply problems that have most clearly harmed patients, said Allen Vaida, an executive vice president of the Institute for Safe Medication Practices, a patient-safety group in Pennsylvania.
In the past two years, Vaida's group has tracked reports of 15 deaths that can be linked to medication shortages.
Nine deaths were reported in Alabama last spring when a shortage of premixed nutrition used in IV-feeding prompted a compounding pharmacy to mix a batch of its own liquid nutrition for patients. The batch became contaminated, Vaida said, leading to the deaths.
Another six deaths have been linked to shortages in anesthesia medicines, Vaida said, when hospitals had little time to train staff how to use unfamiliar alternatives.
"That alternative drug may have a different dose. It may be prepared differently. It may have to be stored differently, and it may have to be administered differently," Vaida said. "If you have 24 to 48 hours to try to educate 200 physicians and 800 nurses on staff, that's almost an impossible task."
Cancer clinics also face problems in reacting to shortages, Vaida said, but the impact on patients can be more difficult to show. That's because some shortages have come with medications that offer only a slightly better chance of short-term cancer survival, Vaida said.
"It's not as cut-and-dried," he said.
A 'TERRIFYING' CLOSE CALL
That's no comfort to cancer patients like Mary McHugh Morrison, 59, of Edina.
Last year, Morrison suffered a relapse of a gynecological cancer, and doctors prescribed a chemotherapy treatment that included a medication called Doxil. Morrison said the treatments seemed to go well for the first four months until she learned three days before her July treatment that her Minnesota Oncology clinic couldn't obtain the drug.
"It was terrifying," she said. "I thought to myself, 'OK, I'm going to look for it.' "
Morrison emailed an old college friend who worked in health care and helped track down a dose of Doxil in Oklahoma. The drug was shipped to Morrison's clinic in Minneapolis, where she received the July treatment a week later than scheduled.
When it became clear that Morrison's clinic might not have Doxil available for her August treatment, she sent out a mass email and found three doses - including one that was about to expire. She received one dose, and other patients at her clinic got the other two.
In September, Morrison found another dose. Her searches for medicine included getting in touch with an old friend from grade school and calling on contacts as far away as California.
"These were doses that were not assigned to patients," Morrison said. Even so, she said, "I felt guilty that I was looking and finding doses and other people didn't even know they could look."
Morrison praised her clinic for being very supportive but had to switch to a new clinic last fall to enroll in a clinical trial. Doctors have taken her off Doxil because one of her tumors started to grow again, and Morrison said she was told the delay in her July treatment was probably a factor.
IMPACT OF DISRUPTIONS
"Why didn't anybody know that these doses were sitting around?" Morrison asked. "There should be a national database so clinics in need of life-saving medications can find sources."
Dr. Cheryl Bailey, an ovarian cancer expert in Minneapolis with Minnesota Oncology, said she could not comment on the particulars of Morrison's story.
Bailey stressed, however, that the Doxil shortage persists. Late last year, the company that manufactures Doxil shut down production because of an equipment problem at an Ohio plant.
With many ovarian cancers, use of Doxil implies that a patient is already undergoing a second or third course of treatment, Bailey said. Usually, she added, that means a cure is unlikely.
Still, Doxil has been an important drug because it has many fewer side effects for some patients, Bailey said. The real difficulty for patients and clinicians came last year, she added, as some patients faced a disruption in the middle of Doxil treatments that can span several months.
"These patients have other options - I don't think anyone is going to die because that particular drug isn't available," Bailey said. "But once you have a cancer and need chemotherapy, you will be very interested in taking a drug like Doxil with minimal side effects."
TRACKING DRUG SUPPLY
Justine and Brian Zirbes are happy that their son Axel received cytarabine when he needed it.
The drug comes in vials that are typically large enough for just one adult but can be split between two small pediatric patients. As Axel's treatment date approached, another child also needed treatment.
Not all kids with cancer were as lucky last year, said Dr. Bruce Bostrom, a pediatric oncologist at Children's. The hospital had to make "some major modifications" in the treatment of about five children with leukemia, Bostrom said, because of the cytarabine shortage (which has since been resolved).
"We're hoping that it didn't affect the outcome of any children," he said. "We may never know....If (the disease) recurs in one patient, you never know if it was going to recur anyway."
Justine Zirbes said she regularly monitors websites and uses social media to learn about shortages, since Axel is still in treatment with other medications.
"We assumed that life-saving drugs would be available all the time," Brian Zirbes said.